Use of gabapentin in the management of post-viral parosmia: a double-blind, randomised, placebo-controlled, multi-site trial
Post-viral Parosmia (distorted smell)
This is a double-blind, randomised, placebo-controlled trial investigating the efficacy of gabapentin in the treatment of parosmia. Participants will be randomised in a 1:1 ratio to receive either gabapentin or placebo. Randomisation will be conducted using a computer-generated sequence via Sealed Envelope, employing permuted-block sequencing. Randomisation will be stratified by baseline parosmia severity (Smell Qx parosmia domain), duration of parosmia, age, gender, and Sniffin’ Sticks Threshold-Discrimination-Identification (TDI) scores to ensure balance across trial arms. Active Intervention (Gabapentin): Participants randomised to the active treatment arm will receive gabapentin capsules (300 mg per capsule) administered orally for a total treatment duration of 8 weeks, followed by a weaning phase. The dosing regimen is as follows: Weeks 1–2: one capsule (300 mg) once daily in the evening; Weeks 3–6: one capsule (300 mg) twice daily, every 12 hours (total daily dose 600 mg); Weeks 7–8 (weaning phase): one capsule (300 mg) once daily in the evening. In total, each participant will receive 84 capsules over the treatment course. Dose adjustments are permitted for tolerability: participants experiencing non-serious side effects such as intolerable daytime drowsiness may reduce to 300 mg once daily; additionally, participants reporting subjective symptomatic improvement by Week 2 (based on the Smell Qx parosmia domain) may elect to remain on 300 mg daily rather than escalating to 600 mg daily. Participants will be supplied with medication in two batches: the first at baseline (Visit 1) and the second at Week 3. Comparator (Placebo): Participants randomised to placebo will receive identically packaged and over-encapsulated placebo capsules, manufactured by Zentiva, matched in appearance, quantity, and dosing schedule to the gabapentin arm. Participants in this arm will follow the same dose-escalation and weaning schedule (Weeks 1–2: one capsule daily; Weeks 3–6: on
1. Participants aged 18–65 years with parosmia secondary to viral infection/COVID-19 infection (≥6 months duration but less than 5 years) 2. Participants must have a Parosmia domain severity score of ≥3/5 on the Smell Qx 3. Participants must have a sniffin stick smell TDI >16.5 4. Participants must be willing able to provide written informed consent 5. Fluent in English and able to understand and complete questionnaires 6. Women of childbearing potential must be willing to use a highly effective method of contraception from consent until end of the trial 7. Female participants of childbearing potential must have a negative urine pregnancy test which will be done at the baseline visit before randomisation and start of trial treatment
1. Participants with known allergies to the odours used in Sniffin Sticks TDI assessment, retronasal olfactory tests or taste strips. 2. Participants with a known allergy to the IMP or its excipients. 3. Parosmia which is primarily associated with chronic sinusitis with or without nasal polyps, allergic rhinitis, sinonasal tumours or other aetiologies. 4. Participants using concurrent medication as listed in Section 8.7. Participants with use of antidepressants/antipsychotics/GABA analogues in the last 12 months. 5. Participants with a history of depression, anxiety, psychosis, self-harm, suicide attempts, or other mental health conditions. 6. Participants who have experienced suicidal or self-harm thoughts within the past month. Participants with any history of neurological conditions e.g. Alzheimer's, Dementia, Parkinsons, Epilepsy, Traumatic Brain Injury or Brain Tumours. 7. Participants with any history of renal failure, dialysis patient, previous renal transplant or known creatinine clearance <30ml/min.* 8. Participants with any history of liver failure, liver disease or previous liver transplant. 9. Participants with a family history of chronic kidney disease, or those currently taking or who have taken a prolonged course (2 weeks or greater) of medications known to affect renal function within the past 6 months, will undergo renal function testing (e.g., creatinine clearance). Medications known to impact renal function include but are not limited too: diuretics such as furosemide, aminoglycosides such as gentamicin, antihypertensives such as ramipril, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, as well as certain antivirals, chemotherapy agents, and calcineurin inhibitors. Individuals with a creatinine clearance of less than 30 mL/min will be excluded from the study. Participants who have comorbidities known to impact renal function such as diabetes, hypertension, cardiovascular disease including previous myocardial infarction, and a